Michele Lupini
Theoretical biophysics of liquid-liquid phase separation in the nucleolus.
Rel. Lamberto Rondoni, Anna Erzberger, Roman Belousov. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Matematica, 2025
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Abstract
Phase separation is a fundamental physical mechanism that drives the organization of many complex systems. Specifically, in biology cells are thought to exploit this mechanism to organize their internal structure and to compartmentalize biochemical processes within membraneless organelles. Nucleoli---one of such organelles in eukaryotes---are known to form hierarchical subcompartments dedicated to ribosomal RNA (rRNA) transcription, processing, and ribosome assembly. The underlying mechanism of these processes and their biological significance remain unknown. Perturbations of rRNA transcription, e.g. in laboratory experiments, reorganises the nucleolar structure. Perturbations of rRNA transcription, e.g. in laboratory experiments, reorganises the nucleolar structure. Quantitative live-cell imaging after inhibition of rRNA transcription reveals two steps of reorganization consisting in, first, fusion of individual subunits, then followed by, second stage, their exposure to the nucleolar surface.
To model the formation of nucleolar subcompartments, we develop a theoretical framework based on Flory-Huggins theory of phase separation in multicomponent solutions and Cahn-Hilliard dynamics
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